Simlukafusp alfa (FAP-IL2v) 是一种免疫细胞因子，经过改造可选择性促进肿瘤微环境中的免疫反应。我们在一项 2 期篮子研究 (NCT03386721) 中评估了 FAP-IL2v 联合 atezolizumab 在复发性和/或转移性宫颈鳞状细胞癌 (SCC) 中的抗肿瘤活性和安全性。 ≥1 种抗癌治疗且患有可测量疾病的患者被纳入。 FAP-IL2v 10 mg 每 3 周一次 (Q3W) 或每周一次 (QW) 给药，持续 4 周，然后每 2 周一次 (Q2W) 与相应的 Q3W 或 Q2W atezolizumab 方案一起给药。主要终点是研究者评估的客观缓解率。共有 48 名患者入组（第 3 周：n = 47；第 3 周/第 2 周：n = 1）。在 45 名可评估疗效的患者中，12 名患者出现客观缓解（27%；CI 16.0-41.0），其中 3 名完全缓解，9 名部分缓解。 6/19 PD-L1 阳性患者（32%；95% CI 15.4-54.0）和 5/24 PD-L1 阴性患者（21%；95% CI 9.2-35.6）出现缓解。中位缓解持续时间为 13.3 个月 (95% CI 7.6-NE)。中位无进展生存期为 3.7 个月（95% CI 3.3-9.0）。不良事件 (AE) 与每种药物的已知安全性一致。 6 名患者 (13%) 发生了导致停用任一药物的 AE。观察到外周血中自然杀伤细胞和 CD8 T 细胞的显着扩增和激活，以及肿瘤浸润和炎症的增加。FAP-IL2v 联合 atezolizumab 具有临床活性，并且在复发性和/或转移性宫颈 SCC 患者中具有可控的安全性。 Hoffmann-La Roche Ltd.版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Simlukafusp alfa (FAP-IL2v) is an immune cytokine engineered to selectively promote immune responses in the tumour microenvironment. We evaluated the antitumour activity and safety of FAP-IL2v plus atezolizumab in recurrent and/or metastatic cervical squamous cell carcinoma (SCC) in a phase 2 basket study (NCT03386721).Patients with confirmed metastatic, persistent or recurrent cervical SCC who had progressed on ≥1 anti-cancer therapy and had measurable disease were enrolled. FAP-IL2v 10 mg was administered once every 3 weeks (Q3W) or once weekly (QW) for 4 weeks then once every 2 weeks (Q2W) with the corresponding Q3W or Q2W atezolizumab regimens. The primary endpoint was objective response rate by investigator assessment.Forty-eight patients were enrolled (Q3W: n = 47; QW/Q2W: n = 1). Among 45 response evaluable patients, objective responses occurred in 12 patients (27%; CI 16.0-41.0), including 3 complete and 9 partial responses. Responses occurred in 6/19 PD-L1 positive patients (32%; 95% CI 15.4-54.0) and 5/24 PD-L1 negative patients (21%; 95% CI 9.2-35.6). Median duration of response was 13.3 months (95% CI 7.6-NE). Median progression-free survival was 3.7 months (95% CI 3.3-9.0). Adverse events (AEs) were consistent with the known safety profile of each drug. AEs leading to withdrawal of either agent occurred in 6 patients (13%). Pronounced expansion and activation of natural killer and CD8 T cells in peripheral blood and increased tumour infiltration and inflammation were observed.FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC.F. Hoffmann-La Roche Ltd.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.